Bacterial infections in cirrhosis are common and associated with increased mortality, but little is known about fungal infections. The aim of this study, a sub-analysis of the Fungal Infection Risk Evaluation study, was to assess the incidence and implications of early invasive fungal disease (IFD) in patients with cirrhosis admitted to intensive care units (ICU). Clinical and laboratory parameters collected in the first 3 days of ICU stay for 782 patients with cirrhosis and/or portal hypertension were analysed and compared with those of 273 patients with very severe cardiovascular disease (CVD). The CVD patients had more co-morbidities and higher APACHE II scores. The overall incidence of IFD was similar in the two groups, but the incidence of IFD in ICU was higher in liver patients (1% versus 0.4%; p 0.025) as was fungal colonization (23.8% versus 13.9%; p 0.001). The ICU and in-hospital mortality, and length of stay were similar in the two groups. A higher proportion of liver patients received antifungal therapy (19.2% versus 7%; p <0.0005). There was no difference in mortality between colonized patients who received antifungal therapy and colonized patients who did not. The incidence of IFD in patients with cirrhosis in ICU is higher compared with another high-risk group, although it is still very low. This risk might be higher in patients with advanced liver disease admitted with acute-on-chronic liver failure, and this should be investigated further. Our data do not support prophylactic use of antifungal therapy in cirrhosis.

BACKGROUND:It is unclear whether the course of cirrhosis and its prognosis are related to the amount of collagen in the liver.AIM:To determine whether fibrosis, assessed by collagen proportionate area (CPA) in patients with compensated cirrhosis, is associated with the presence of oesophageal varices, and predict disease decompensation during the follow-up period.METHODS:We prospectively evaluated 118 consecutive patients with compensated cirrhosis to correlate fibrosis, assessed by CPA in liver biopsies, with the presence of oesophageal varices (OV) and with the rate of liver decompensation (LD) development during a median follow-up of 72 months.RESULTS:At baseline 38 (32.2%) patients had OV and during the follow-up (median 72 months, IQR 47-91), 17 patients (14.4%) developed LD. The mean CPA value was different in patients with and without OV (14.8 ± 5.9% vs. 21.6 ± 9.5%, P < 0.001). The best CPA cut-off for OV by area under the receiver operating characteristic (AUROC) was ≥14% and with multivariate logistic analysis CPA was the only variable associated with OV (OR: 28.32, 95% CI: 6.30-127.28; P < 0.001). By AUROC analysis the best CPA cut-off to predict LD was 18.0%. By Cox regression multivariate analysis CPA ≥18% (HR: 3.99, 95% CI: 1.04-11.45; P = 0.036), albumin (HR: 0.12, 95% CI: 0.04-0.43; P = 0.001) and presence of OV (HR: 8.15, 95% CI: 2.31-28.78; P = 0.001) were independently associated with LD.CONCLUSION:Quantification of fibrosis by collagen proportionate area allows identification of patients with compensated HCV cirrhosis with a higher likelihood of clinically relevant portal hypertension and a higher risk of decompensation.

of overt hepatic encephalopathy (HE) and associated with poor prognosis. Preliminary studies showed improvement in cognitive functions and HRQOL with nutritional supplementation in MHE but there is no study on nutritional management in patients with MHE. We assessed the effects of nutritional therapy on cognitive functions and HRQOL in patients of cirrhosis with MHE. Methods: Consecutive patients of cirrhosis with MHE were randomized to group A received nutritional therapy (30–35kcal/kg/day and 1.0–1.5 gram of vegetable protein/kg/day) and group B on no nutritional therapy (diet as patient was taking before) for 6 months. MHE was diagnosed based on psychometry hepatic encephalopathy score (PHES) and HRQOL assessed by Sickness impact profile (SIP) questionnaire. Primary endpoints were improvement or worsening in MHE and improvement in HRQOL. Results: 120 patients were randomized into two groups; group-A (n = 60, age 42.1±10.3 yr, 48 men) and group-B (n = 60, age 42.4±9.6 yr, 47 men). There was no significant difference in baseline characteristics between the two groups. Baseline PHES (−8.12±1.32 vs −8.53±1.38; p = 0.08) and SIP score (14.25±5.8 vs 15.44±5.03; p = 0.85) were similar in both the groups. Reversal of MHE was higher in group A (71.1% vs 22.8%; p =0.001) and improvement in HRQOL was also higher in group A (D SIP 3.24±3.63 vs 0.54±3.58; p = 0.001) compared to group B. Conclusions: Nutritional therapy is effective in treatment of MHE and associated with improvement in HRQOL.

Background: Adrenal insufficiency is often present in cirrhosis. We hypothesize that a prolonged adrenocorticotropic hormone (ACTH) stimulus can restore cellular capacity of adrenal glands to secrete cortisol. Aim of our study was to assess adrenal responsiveness to prolonged ACTH stimulation in cirrhotics.Methods: Prospective observational study in 121 consecutively admitted cirrhotic patients undergoing a low dose short synacthen test and plasma ACTH measurement using a chemiluminescence immunoassay. Long synacthen test was performed if the low dose was abnormal.Results: 46 patients had abnormal low dose short test (38%), and 29 underwent the long test: 41% showed normal response (Group 1), 55% showed delayed response (Group 2) and 1 had abnormal response (4%). Baseline ACTH levels did not significantly differ between the two groups. Median basal cortisol was higher in Group 1 (296 vs. 198 nmol/L; p = 0.02). Using ROC curve basal cortisol <254 nmol/L was associated with a delayed long synacthen test response (AUC 0.78, p = 0.001) with good accuracy (sensitivity 67%, specificity 81%).Conclusion: A delayed cortisol response after a prolonged ACTH stimulation is found in over fifty percent of cirrhotics with abnormal low dose short synacthen test, confirming that the mechanism of hypoadrenalism in these patients could be related both to adrenal cellular dysfunction and hypothalamus-pituitary adrenal axis impairment. (c) 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Introduction: Outcomes in primary biliary cirrhosis (PBC) can be predicted by biochemical response to ursodeoxycholic acid (UDCA). However, existing definitions do not take the stage of the liver disease into account and dichotomize UDCA response and long-term risk whereas both are a continuum. We analyzed the UK-PBC Research Cohort to develop a risk score that includes markers of disease stage, as well as post-treatment liver biochemistries modeled as continuous variables.

BACKGROUND:Natural immunity against cytomegalovirus (CMV) can control virus replication after solid organ transplantation; however, it is not known which components of the adaptive immune system mediate this protection. We investigated whether this protection requires human leukocyte antigen (HLA) matching between donor and recipient by exploiting the fact that, unlike transplantation of other solid organs, liver transplantation does not require HLA matching, but some donor and recipient pairs may nevertheless be matched by chance. METHODS:To further investigate this immune control, we determined whether chance HLA matching between donor (D) and recipient (R) in liver transplants affected a range of viral replication parameters. RESULTS:In total, 274 liver transplant recipients were stratified according to matches at the HLA A, HLA B, and HLA DR loci. The incidence of CMV viremia, kinetics of replication, and peak viral load were similar between the HLA matched and mismatched patients in the D+/R+ and D-/R+ transplant groups. D+/R- transplants with 1 or 2 mismatches at the HLA DR locus had a higher incidence of CMV viremia >3000 genomes/mL blood compared to patients matched at this locus (78% vs. 17%; P = 0.01). Evidence was seen that matching at the HLA A locus had a small effect on peak viral loads in D+/R- patients, with median peak loads of 3540 and 14,706 genomes/mL in the 0 and combined (1 and 2) mismatch groups, respectively (P = 0.03). CONCLUSION:Overall, our data indicate that, in the setting of liver transplantation, prevention of CMV infection and control of CMV replication by adaptive immunity is minimally influenced by HLA matching of the donor and recipient. Our data raise questions about immune control of CMV in the liver and also about the cells in which the virus is amplified to give rise to CMV viremia.

P0386 PREDICTING LIVER DECOMPENSATION AFTER RESECTION FOR HEPATOCELLULAR CARCINOMA: A RECURSIVE PARTITIONING ANALYSIS OF PROGNOSTIC FACTORS D. Citterio, C. Sposito, A. Facciorusso, M. Flores Reyes, M. Mazzola, V. Mazzaferro. Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, National Cancer Institute (Istituto Nazionale Tumori), Milan, Gastroenterology Unit, University of Foggia, Foggia, Italy E-mail: davide.citterio@istitutotumori.mi.it

Introduction Cirrhosis is a complex acquired disorder of coagulation with a recent paradigm shift in understanding to consider cirrhosis as a pro-thrombotic disorder. It is a frequent indication for transfusion of blood components, both for prophylaxis and for treatment of bleeding, although indications and patterns of blood use are poorly characterised. Methods All NHS trusts with representation on the BSG membership list were invited to take part in a national audit. Data were collected prospectively on conseutive admissions with a confirmed diagnosis of liver cirrhosis over a 4 week period, with follow up to discharge/death/day 28. Specific information was requested on use of blood components, including indication, type of component and laboratory indices prior to transfusion. Standards were defined against guidelines on the use of red blood cells (RBCs), fresh frozen plasma (FFP), platelets and cryoprecipitate. Results Data on 1313 consecutive patients with cirrhosis (mean age 58 years, 65% male) were collected from 85 hospitals. The predominant aetiology was alcohol (70%; 921/1313); 74% of admissions were for features of decompensation; and 21% (275/1313) cases had a positive septic screen. 30% (391/1313) of all admissions were transfused a blood component; in 61% (238/391) this was for treatment of bleeding and in 39% (153/391) for prophylaxis. In patients transfused for bleeding (81%, 192/238 for gastrointestinal bleeding), 92% (220/238) received RBCs, 32% (77/238) FFP, 14% (34/238) platelets and 4% (10/238) cryoprecipitate; in patients with bleeding who received RBCs, the Hb threshold was >8 g/dL prior to RBC transfusion in 31% (69/220) cases. For prophylaxis the majority (61%, 94/153) received transfusion in the absence of a planned procedure. In patients transfused for prophylaxis prior to a procedure (59/153): 19% (3/16) received FFP at an INR ≤1.5 for high risk procedures and 33% (6/18) received FFP at an INR ≤2 for low risk procedures; 36% (9/25) received platelet transfusion at a platelet count >50 prior to a procedure. The most frequent procedures resulting in prophylactic transfusion were paracentesis (18/59), surgery (15/59) and endoscopy (10/59). In-hospital venous thromboembolism was documented in 2% (29/1313) cases. Case fatality during follow up was 10% overall (128/1313) with decompensated cirrhosis (41%; 52/128) as the most frequent cause of death. Conclusion Patients with cirrhosis are frequently transfused during hospitalisation. This audit highlights areas where greater scrutiny of blood component use is required, particularly in the group transfused for prophylaxis of bleeding. Further work is needed to improve patterns of blood use in cirrhosis to ensure patients are not exposed to unnecessary transfusion and its attendant harms. Disclosure of Interest None Declared.

of 73% (56/77). No deaths occurred; no clinically meaningful differences were observed in frequencies of serious adverse events (AEs), AEs leading to discontinuation, or grade 3/4 AST/ALT elevations in patients with or without cirrhosis. Conclusions: All-oral DCV+ASV treatment exhibited similarly high SVR rates and no clinically relevant differences in safety/tolerability in cirrhotic and non-cirrhotic patients with HCV genotype 1b infection.

volume per IBW (SV/IBW) correlated closely with CE in the HALT-C trial. We enlarge on this experience by assessing test deterioration (D) on prediction of CE. Data on N=223 HALT-C trial participants (Hepat;55:1019) in the Quantitative liver function test ancillary study were analyzed to assess the association between M24 QLSS tests and deterioration from baseline to the time to first CE (18 CE in 83 patients). Methods: CE = CTP score 7, variceal bleeding, ascites, encephalopathy, liver-death. Non-CE = transplantation, HCC, presumed HCC, and non-hepatic deaths. Patients were at risk from M24 (entry) to first CE or non-CE. Patients were evaluated every 3 months with maximal follow-up of 6 years (median 5.5 years). QLSS: PHM = (LSI + LBI)/2, SV/IBW (cc/kg), EPSA = {(4.342 − 2.008RR − 0.0209PHM + 18.15/R) + sqrt[313/(R + 0.5L) − logRR−9.6])/2, where RR (redistribution ratio) = [(Lp/Sp/2.5) + (Lp/BMp/17.5)]/2 and where, in planar counts, Lp, Sp, BMp, R = R lobe length, L = L lobe length} (Hep22:1113). Results: In univariate analyses, PHM, SV/IBW, and EPSA were significantly (p < 0.0001) associated with risk of CE by unadjusted analysis. Deterioration (D) from baseline was also significantly associated with CE for PHM (D-PHM) (p =0.0016) and EPSA (D-EPSA) (p = 0.051), but not SV/IBW (p=0.400). Multivariate Cox model analysis confined to PHM with D-PHM and EPSA with D-EPSA showed that both independently correlated significantly (PHM: p < 0.0001 and <0.0001, EPSA: p < 0.0001, 0.0079) with CE. Conclusions: 1. Hepatic dysfunction (PHM/EPSA) and SV/IBW predict subsequent CE. 2. Deterioration of hepatic function independently predicted CE.